Prostate Cancer: Diagnosis and evaluation: Difference between revisions

 
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[[Category:Prostate Cancer]]
[[Category:Prostate Cancer]]
'''See [[AUA: Early Detection of Prostate Cancer (2023)|2023 AUA Guidelines on Early Detection of Prostate Cancer]]'''


'''Includes [https://pubmed.ncbi.nlm.nih.gov/33661093/ 2021 CUA Best Practice Report on PET/CT and PET/MR in Prostate Cancer]'''
'''Includes [https://pubmed.ncbi.nlm.nih.gov/33661093/ 2021 CUA Best Practice Report on PET/CT and PET/MR in Prostate Cancer]'''
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* '''Labs'''
* '''Labs'''
** '''PSA'''
** '''PSA'''
*** '''A newly elevated PSA value should be repeated if no prior PSA or current value inconsistent with previous trend'''
* '''Imaging'''
* '''Imaging'''
** '''MRI'''
** '''MRI'''
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*#*** '''Is a TRUS biopsy of benefit in a 95 year-old male with a PSA 400 ng/mL ?'''
*#*** '''Is a TRUS biopsy of benefit in a 95 year-old male with a PSA 400 ng/mL ?'''
*#** '''Is the patient a candidate for treatment ([[AUA: Clinically Localized Prostate Cancer (2017)|contraindications to radiotherapy]], for example)?'''
*#** '''Is the patient a candidate for treatment ([[AUA: Clinically Localized Prostate Cancer (2017)|contraindications to radiotherapy]], for example)?'''
*#** '''<span style="color:#ff0000">Family history of</span> [[Prostate Cancer: Epidemiology and Pathogenesis|BRCA/Lynch syndrome cancers]] <span style="color:#ff0000">may prompt genetic screening in patient</span>'''
*#** '''<span style="color:#ff0000">Family history</span>'''
*#***'''<span style="color:#ff0000">Criteria for "strong" family history (2):</span>'''
*#***# '''<span style="color:#ff0000">≥1 brother or father OR ≥2 male relatives with one of the following (3):</span>'''
*#***##'''<span style="color:#ff0000">Diagnosed with prostate cancer at age <60 years</span>'''
*#***##'''<span style="color:#ff0000">Any of whom died of prostate cancer</span>'''
*#***##'''<span style="color:#ff0000">Any of whom had metastatic prostate cancer.</span>'''
*#***# '''<span style="color:#ff0000">Family history of other cancers with ≥2 cancers in hereditary breast and ovarian cancer syndrome or Lynch syndrome spectrum.</span>'''
*#***#* '''<span style="color:#ff0000">Hereditary breast and ovarian cancer syndrome</span>'''
*#***#**'''<span style="color:#ff0000">Associated cancers (5):[https://www.ncbi.nlm.nih.gov/books/NBK1247/]</span>'''
*#***#*#'''<span style="color:#ff0000">Breast (male and female)</span>'''
*#***#*#'''<span style="color:#ff0000">Ovarian</span>'''
*#***#*#'''<span style="color:#ff0000">Prostate</span>'''
*#***#*#'''<span style="color:#ff0000">Pancreatic</span>'''
*#***#*#'''<span style="color:#ff0000">Melanoma</span>'''
*#***#*'''<span style="color:#ff0000">Lynch syndrome</span>'''
*#***#**'''<span style="color:#ff0000">Associated cancers (11)</span>[https://www.ncbi.nlm.nih.gov/books/NBK431096/]'''
*#***#**#'''<span style="color:#ff0000">Colorectal (20-80%) (most common)</span>'''
*#***#**#'''<span style="color:#ff0000">Gynecologic</span>'''
*#***#**## '''<span style="color:#ff0000">Endometrial (15-60%) in females (second most common)</span>'''
*#***#**##'''<span style="color:#ff0000">Ovarian cancer (1-38%) in females</span>'''
*#***#**#'''<span style="color:#ff0000">Urologic</span>'''
*#***#**##'''<span style="color:#ff0000">Urothelial (1-18%), includes upper urinary tract and bladder</span>'''
*#***#**##'''<span style="color:#ff0000">Prostate</span>'''
*#***#**##'''<span style="color:#ff0000">Adrenal[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739861/ §]</span>'''
*#***#**#'''<span style="color:#ff0000">Other gastrointestinal</span>'''
*#***#**##'''<span style="color:#ff0000">Gastric cancers (1-13%)</span>'''
*#***#**##'''<span style="color:#ff0000">Hepatobiliary</span>'''
*#***#**##'''<span style="color:#ff0000">Small bowel</span>'''
*#***#**#'''<span style="color:#ff0000">Skin</span>'''
*#***#**#*'''<span style="color:#ff0000">Sebaceous adenoma, sebaceous epithelioma, sebaceous adenocarcinoma, keratoacanthoma, and squamous cell carcinoma[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423888/]</span>'''
*#***#**# '''<span style="color:#ff0000">Brain</span>'''
*#***#**#'''<span style="color:#ff0000">Inconsistent: Pancreas, breast, (prostate)</span>'''
*#**'''<span style="color:#ff0000">Patients with a "strong" family history should ideally be genotyped</span>[https://pubmed.ncbi.nlm.nih.gov/37096582/]'''
*#***'''Genotype is to ascertain whether there is presence of a pathogenic variant (e.g., BRCA1/2, Lynch Syndrome, ATM, CHEK2) or one or more of a growing set of identified germline DNA damage-repair mutations found in patients with metastatic prostate cancer diagnoses.'''
*# '''Patient preference for investigations/treatment'''
*# '''Patient preference for investigations/treatment'''
*#* '''Benefits/harms of treatment (sexual function, for example)'''
*#* '''Benefits/harms of treatment (sexual function, for example)'''
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** '''<span style="color:#ff0000">Digital rectal examination</span>'''
** '''<span style="color:#ff0000">Digital rectal examination</span>'''
*** '''A palpable tumour and the extent is associated with local disease extent (clinical T stage)'''
*** '''A palpable tumour and the extent is associated with local disease extent (clinical T stage)'''
*** '''In a screened population, an abnormal DRE is also associated with an increased risk for detecting high-grade (Gleason 8 to 10) prostate cancer'''
****'''Can both overestimate and underestimate the extent of disease because of its poor sensitivity and lack of reproducibility'''
*** '''Can both overestimate and underestimate the extent of disease because of its poor sensitivity and lack of reproducibility'''
***** '''Consider useful to detect presence, but not useful to assess stage'''
*** '''Consider useful to detect presence, but not useful to assess stage'''
*** '''In a screened population, an abnormal DRE is associated with an increased risk for detecting high-grade (Gleason 8 to 10) prostate cancer'''
*** '''When DRE and PSA tests are used in prostate cancer screening, detection rates are higher with PSA testing alone vs. DRE alone, and highest with the tests together'''
***'''<span style="color:#ff0000">Indications (2023 AUA Guidelines on Early Detection of Prostate Cancer[https://pubmed.ncbi.nlm.nih.gov/23659877/])</span>'''
**** '''See below in Labs/PSA/Landmark Studies'''
****'''<span style="color:#ff0000">Screening</span>'''
**** '''The [[AUA: Prostate Cancer Screening (2018)|2018 AUA]] and [[CUA: Prostate Cancer Screening (2017)|2017 CUA]] Guidelines support the role of DRE in screening'''
*****'''<span style="color:#ff0000">Should not use DRE as the sole screening method.</span>'''
******'''The primary screening modality recommended for the early detection of prostate cancer is a PSA blood test.'''
*****'''<span style="color:#ff0000">Insufficient evidence to support adding DRE to PSA-based prostate cancer screening.</span>'''
******For various reasons, clinicians may choose to complement PSA screening with DRE based on SDM.
*******When DRE and PSA tests are used in prostate cancer screening, detection rates are higher with PSA testing alone vs. DRE alone, and highest with the tests together[https://pubmed.ncbi.nlm.nih.gov/28012755/]
*****[[AUA: Prostate Cancer Screening (2018)|2018 AUA]] and [[CUA: Prostate Cancer Screening (2017)|2017 CUA]] Guidelines support the role of DRE in screening
****'''<span style="color:#ff0000">Elevated PSA[https://pubmed.ncbi.nlm.nih.gov/23659877/]</span>'''
*****'''<span style="color:#ff0000">If PSA ≥ 2 ng/mL, strongly consider supplementary DRE to establish risk of clinically significant prostate cancer.</span>'''
******Highest utility of DRE in randomized trials is demonstrated in the workup of patients with an elevated PSA.*******In contrast to a screening application, use of DRE subsequent to the screening encounter may be of value.
********In patients undergoing prostate biopsy for an elevated PSA during screening, abnormal DRE improves the PPV for any prostate cancer and GG2+ detection


=== <span style="color:#ff0000">Labs</span> ===
=== <span style="color:#ff0000">Labs</span> ===


==== PSA ====
==== PSA[https://pubmed.ncbi.nlm.nih.gov/12525533/] ====
* '''<span style="color:#ff0000">Serum PSA is the single test with the highest positive predictive value for prostate cancer</span>'''
* '''<span style="color:#ff0000">Serum PSA is the single test with the highest positive predictive value for prostate cancer</span>'''
**'''Although as many as 20-30% of males evaluated for an elevated PSA level may be diagnosed with prostate cancer after TRUS biopsy, as many as 70-80% will not be found to have cancer'''
**'''Although as many as 20-30% of males evaluated for an elevated PSA level may be diagnosed with prostate cancer after TRUS biopsy, as many as 70-80% will not be found to have cancer'''
*'''<span style="color:#ff0000">PSA Basics</span>'''
*'''<span style="color:#ff0000">If newly elevated PSA (no prior PSA or current value inconsistent with previous trend), then repeat the PSA prior to a secondary biomarker, imaging, or biopsy.</span>'''
**Discovered in 1979
**'''In people with a newly elevated PSA, it will return to a normal level in 25-40% upon retesting.'''
**'''<span style="color:#ff0000">Member of kallikrein gene family</span>'''
**'''<span style="color:#ff0000">An enzyme (serine protease) which functions to liquify semen</span>'''
**Molecular weight: 33-kD
***'''Begins as''' 17-amino acid chain '''preproPSA''' --> '''cleavage results in inactive proPSA --> cleavage''' by hK2 '''results in active form PSA'''
**Primarily produced by prostatic luminal epithelial cells
*** Has been detected in other body fluids and tissues: in females, PSA is found in female ejaculate at concentrations roughly equal to that found in male semen; other fluids with high concentrations of PSA include breast milk and amniotic fluid.
***'''Ectopic expression of PSA occurs in normal breast tissue, and tumours of the adrenals, kidneys, colon, ovaries, liver, and parotid[https://pubmed.ncbi.nlm.nih.gov/7536238/]'''
** '''<span style="color:#ff0000">Expression is strongly influenced by androgens; becomes detectable at puberty with increasing levels of luteinizing hormone and testosterone</span>'''
***'''<span style="color:#ff0000">Clinical implication: in hypogonadal men with low testosterone levels, serum PSA level may be low because of decreased expression and may not reflect the presence of prostate disease such as cancer</span>'''
**'''<span style="color:#ff0000">Half-life: 2-3 days</span>[https://pubmed.ncbi.nlm.nih.gov/9555548/][https://pubmed.ncbi.nlm.nih.gov/8973698/]'''
**'''<span style="color:#ff0000">Half-life: 2-3 days</span>[https://pubmed.ncbi.nlm.nih.gov/9555548/][https://pubmed.ncbi.nlm.nih.gov/8973698/]'''
**'''<span style="color:#ff0000">Circulates in bound/complexed (70-80%) and unbound/free (20-30%) forms</span>'''
**'''A repeat PSA in a few months is recommended, though it can be shortened or lengthened depending on other clinical factors.'''
*** '''<span style="color:#ff0000">Bound/complexed PSA</span>'''
****'''<span style="color:#ff0000">Proteins that bind PSA in blood (3):</span>'''
****#'''<span style="color:#ff0000">α1-antichymotripson</span> (ACT)'''
****#* '''<span style="color:#ff0000">Binds most PSA in an irreversible fashion</span>'''
****#* Detectable form of bound PSA
****# '''<span style="color:#ff0000">α2-macroglobulin</span> (A2M)'''****#*'''Binds 5-10% of PSA'''
****#*'''PSA-A2M complex undetectable by most current assays'''
****#'''<span style="color:#ff0000">α1-protease inhibitor</span> (API)'''
****#*'''Binds 1-2% of PSA'''
****#*Detectable form of bound PSA (to a lesser extent than PSA bound to ACT)
***'''<span style="color:#ff0000">Free PSA</span>'''
****'''Rendered inactive within the prostatic epithelial cell before release into the serum'''
****'''<span style="color:#ff0000">Isoforms (3):</span>'''
****#'''<span style="color:#ff0000">Intact PSA</span>'''
****#'''<span style="color:#ff0000">BPH-associated PSA (BPSA)</span>'''
****#*'''Generally limited to transition zone tissue'''
****#'''<span style="color:#ff0000">proPSA</span>'''
****#*'''<span style="color:#ff0000">Uncleaved free PSA molecule with a leader sequence</span>''' (see above)
****#*Evaluated as a marker with conflicting results
****#*'''Exists in 3 forms: -2proPSA, -4proPSA, -7proPSA'''
****#'''Normally, these isoforms exist in equal concentrations'''
****#*'''BPSA is highly expressed in BPH'''
****#*'''proPSA is highly expressed in prostate cancer'''


===== Causes of elevated PSA =====
===== Causes of elevated PSA =====
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**** '''<span style="color:#ff0000">Prostate cancer lacks basal cells</span>, resulting in the disruption of the basement membrane and normal lumen architecture'''
**** '''<span style="color:#ff0000">Prostate cancer lacks basal cells</span>, resulting in the disruption of the basement membrane and normal lumen architecture'''
*** '''<span style="color:#ff0000">PSA levels are inversely correlated with risks of</span>'''  
*** '''<span style="color:#ff0000">PSA levels are inversely correlated with risks of</span>'''  
****'''<span style="color:#ff0000">Pathologically organ-confined disease</span>'''
****'''<span style="color:#ff0000">Pathologically organ-confined (pT2) disease</span>'''
***** '''<span style="color:#ff0000">PSA < 4.0 ng/mL: 80%</span>'''
***** '''<span style="color:#ff0000">PSA < 4.0 ng/mL: 80%</span>'''
***** '''<span style="color:#ff0000">PSA 4-10 ng/mL: 66%</span>'''
***** '''<span style="color:#ff0000">PSA 4-10 ng/mL: 66%</span>'''
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***** '''PSA >50 ng/mL: 75%'''
***** '''PSA >50 ng/mL: 75%'''
*'''<span style="color:#ff0000">Prostate manipulation</span>'''
*'''<span style="color:#ff0000">Prostate manipulation</span>'''
**'''<span style="color:#ff0000">May influence PSA in a clinically meaningful way</span>'''
**'''<span style="color:#ff0000">May influence PSA in a clinically meaningful way[https://pubmed.ncbi.nlm.nih.gov/23659877/]</span>'''
**#'''<span style="color:#ff0000">Biopsy</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#'''<span style="color:#ff0000">Urinary tract infections</span>'''
**#*'''Results in immediate elevation in the serum PSA level, with a median increase of 6-8 ng/mL'''
**#'''<span style="color:#ff0000">Instrumentation (e.g., prostate biopsy, cystoscopy, urinary retention, recent bladder catheterization)</span>'''
**#*'''Usually returns to a stable, baseline level within 2-3 weeks'''
**##'''<span style="color:#ff0000">Biopsy</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#'''<span style="color:#ff0000">TURP</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**##*'''Results in immediate elevation in the serum PSA level, with a median increase of 6-8 ng/mL'''
**#*'''Results in immediate elevation in the serum PSA level, with a median increase of 6-13 ng/mL[https://pubmed.ncbi.nlm.nih.gov/7691013/]'''
**##*'''Usually returns to a stable, baseline level within 2-3 weeks'''
**#*'''Usually returns to a stable, baseline level within 2-3 weeks[https://pubmed.ncbi.nlm.nih.gov/7691013/]'''
**##'''<span style="color:#ff0000">Cystoscopy</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**# '''<span style="color:#ff0000">Ejaculation</span>'''  
**##*Studies have found that cystoscopy results in small (0.05-0.15 ng/mL) increase in PSA and have suggested that serum PSA determination after either a flexible or a rigid cystoscopy is accurate and reliable
**#*'''Studies examining the effect of ejaculation on serum PSA have reported conflicting results.'''
**##'''<span style="color:#ff0000">TURP</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#*'''<span style="color:#ff0000">A repeat PSA test after 48 hours of sexual abstinence may be helpful for interpreting serum PSA levels that are minimally elevated or newly elevated.</span>'''
**##*'''Results in immediate elevation in the serum PSA level, with a median increase of 6-13 ng/mL[https://pubmed.ncbi.nlm.nih.gov/7691013/]'''
**# '''<span style="color:#ff0000">Long-distance cycling</span>'''
**##*'''Usually returns to a stable, baseline level within 2-3 weeks[https://pubmed.ncbi.nlm.nih.gov/7691013/]'''
**#*'''PSA levels increasing by ≈10% after bicycle rides > 55km'''
**##'''<span style="color:#ff0000">Recent bladder catheterization</span>'''
**'''<span style="color:#ff0000">Unlikely to influence PSA in a clinically meaningful way'''
**##*One study found very little effect on PSA level at day 1 and 3 after catheterization and suggested that routine evaluation PSA in patients with recent catheterization.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393098/]
**'''<span style="color:#ff0000">Unlikely to influence PSA in a clinically meaningful way[https://pubmed.ncbi.nlm.nih.gov/23659877/]'''
**#'''<span style="color:#ff0000">DRE</span>'''  
**#'''<span style="color:#ff0000">DRE</span>'''  
**#*'''Can lead to slight increases in serum PSA level; however, the resultant change in PSA values falls within the error of the assay and''' '''<span style="color:#ff0000">rarely causes false-positive test results</span>'''
**#*'''Can lead to slight increases in serum PSA level; however, the resultant change in PSA values falls within the error of the assay and''' '''<span style="color:#ff0000">rarely causes false-positive test results</span>'''
**#'''<span style="color:#ff0000">Cystoscopy</span>[https://pubmed.ncbi.nlm.nih.gov/7691013/][https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#'''<span style="color:#ff0000">Bicycle riding</span>'''
**#*'''Results in small (0.05-0.15 ng/mL) increase in PSA'''
**#*With long-distance (> 55km) bicycle rides, PSA levels increasing by ≈10%
**#*'''Serum PSA determination after either a flexible or a rigid cystoscopy is accurate and reliable'''
**#'''<span style="color:#ff0000">Ejaculation</span>'''
**#*'''Studies examining the effect of ejaculation on serum PSA have reported conflicting results.'''
**#**Most controlled studies evaluating ejaculation suggest it either does not significantly impact or modestly increases (~10%) PSA.
**#*'''<span style="color:#ff0000">A repeat PSA test after 48 hours of sexual abstinence may be helpful for interpreting serum PSA levels that are minimally elevated or newly elevated.</span>'''
**#'''<span style="color:#ff0000">TRUS</span>[https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#'''<span style="color:#ff0000">TRUS</span>[https://pubmed.ncbi.nlm.nih.gov/10376076/]'''
**#*'''Results in small (0.3 ng/mL) increase in PSA'''
**#*'''Results in small (0.3 ng/mL) increase in PSA'''
**#*'''Serum PSA determination after TRUS without biopsy is accurate and reliable'''
**#*'''Serum PSA determination after TRUS without biopsy is accurate and reliable'''
**# '''<span style="color:#ff0000">Urethral catheterization</span>'''
**#*'''Very little effect on PSA level'''
**#*'''In patients with urethral catheter, routine evaluation of PSA rising should be considered.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393098/]'''
**'''Most of the rise in total PSA after prostate manipulation is contributed by the free (non-bound) component.'''
**'''Most of the rise in total PSA after prostate manipulation is contributed by the free (non-bound) component.'''
*** '''In general, complexed PSA is the most stable component and relatively little rise occurs following prostate manipulation.'''
*** '''In general, complexed PSA is the most stable component and relatively little rise occurs following prostate manipulation.'''
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**#'''<span style="color:#ff0000">Visualization of zonal and anatomical features of the prostate.</span>'''
**#'''<span style="color:#ff0000">Visualization of zonal and anatomical features of the prostate.</span>'''
**#*See [https://www.researchgate.net/figure/Zonal-prostate-anatomy-on-axial-T2-weighted-MRI-image-peripheral-zone-PZ-and_fig1_346570342 Figure]
**#*See [https://www.researchgate.net/figure/Zonal-prostate-anatomy-on-axial-T2-weighted-MRI-image-peripheral-zone-PZ-and_fig1_346570342 Figure]
**#'''<span style="color:#ff0000">Optimal sequence in establishing the anatomic relation of the tumor with critical structures, such as the prostatic capsule and neurovascular bundles</span>'''.[https://pubmed.ncbi.nlm.nih.gov/26594835/]
**#'''<span style="color:#ff0000">Optimal sequence to evaluate lesions in the transition zone[https://pubmed.ncbi.nlm.nih.gov/31392526/]</span>'''
**#'''<span style="color:#ff0000">Optimal sequence to evaluate lesions in the transition zone[https://pubmed.ncbi.nlm.nih.gov/31392526/]</span>'''
**#'''Optimal sequence in establishing the anatomic relation of the tumor with critical structures, such as the prostatic capsule and neurovascular bundles'''.[https://pubmed.ncbi.nlm.nih.gov/26594835/]
** '''<span style="color:#ff0000">Signal intensity</span>'''  
** '''<span style="color:#ff0000">Signal intensity</span>'''  
***'''<span style="color:#ff0000">High intensity</span>'''
***'''<span style="color:#ff0000">High intensity</span>'''
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****'''<span style="color:#ff0000">Fat</span>'''
****'''<span style="color:#ff0000">Fat</span>'''
****'''<span style="color:#ff0000">Normal peripheral zone (due to its high water content)</span>'''
****'''<span style="color:#ff0000">Normal peripheral zone (due to its high water content)</span>'''
****'''Seminal vesicles'''
****'''<span style="color:#ff0000">Seminal vesicles</span>'''
***'''Intermediate intensity'''
***'''Intermediate intensity'''
****'''Central zone'''
****'''Central zone'''
*****Clinical implication: differential diagnosis of intermediate/low intensity lesions on T2 at the base of prostate and paramedian includes central zone that is being pushed out by BPH nodules of transition zone or cancer
*****Clinical implication: differential diagnosis of intermediate/low intensity lesions on T2 at the base of prostate and paramedian includes central zone that is being pushed out by BPH nodules of transition zone or cancer
***'''<span style="color:#ff0000">Low intensity (7):</span>'''
***'''<span style="color:#ff0000">Low intensity (7): </span><span style="color:#0000ff">CHAPPSS</span>'''
***#'''<span style="color:#ff0000">Prostate cancer</span>'''
***#'''<span style="color:#ff0000">Prostate </span><span style="color:#0000ff">C</span><span style="color:#ff0000">ancer</span>'''
***#*As 70% of all prostate cancers occur within the peripheral zone, the tissue characteristics allow for T2WI to detect a significant number of tumors in this zone
***#*As 70% of all prostate cancers occur within the peripheral zone, the tissue characteristics allow for T2WI to detect a significant number of tumors in this zone
***#*
***#*
***#'''<span style="color:#ff0000">Hemorrhage</span>'''
***#'''<span style="color:#0000ff">H</span><span style="color:#ff0000">emorrhage</span>'''
***#*Post-biopsy hemorrhage can interfere with tumor detection[https://pubmed.ncbi.nlm.nih.gov/26594835/], since areas of hemorrhage appear similar to cancer on T2WI
***#*Post-biopsy hemorrhage can interfere with tumor detection[https://pubmed.ncbi.nlm.nih.gov/26594835/], since areas of hemorrhage appear similar to cancer on T2WI
***#**If obtaining prostate MRI post-biopsy, a delay of 6-8 weeks after biopsy is recommended; but even with this delay, significant hemorrhage may be discovered, and, if present, the examination should be rescheduled[https://pubmed.ncbi.nlm.nih.gov/26594835/]
***#**If obtaining prostate MRI post-biopsy, a delay of 6-8 weeks after biopsy is recommended; but even with this delay, significant hemorrhage may be discovered, and, if present, the examination should be rescheduled[https://pubmed.ncbi.nlm.nih.gov/26594835/]
***#*Can be distinguished from cancer with T1WI (hemorrhage has high intensity on T1WI, cancer has low intensity on T2WI)
***#*Can be distinguished from cancer with T1WI (hemorrhage has high intensity on T1WI, cancer has low intensity on T2WI)
***#'''<span style="color:#ff0000">Prostatitis</span>'''
***#'''<span style="color:#0000ff">A</span><span style="color:#ff0000">trophy</span>'''
***#'''<span style="color:#ff0000">Atrophy</span>'''
***#'''<span style="color:#0000ff">P</span><span style="color:#ff0000">rostatitis</span>'''
***#'''<span style="color:#ff0000">Scars</span>'''
***#'''<span style="color:#0000ff">P</span><span style="color:#ff0000">ost-treatment changes</span>'''
***#'''<span style="color:#ff0000">Post-treatment changes</span>'''
***#'''<span style="color:#0000ff">S</span><span style="color:#ff0000">cars</span>'''
***#'''<span style="color:#ff0000">Stromal hyperplasia i.e. benign prostatic hyperplasia (BPH)</span>'''
***#'''<span style="color:#0000ff">S</span><span style="color:#ff0000">tromal hyperplasia i.e. benign prostatic hyperplasia (BPH)</span>'''
***#*'''Clinical implication: On T2WI, BPH nodules can be difficult to distinguish from cancer'''
***#*'''Clinical implication: On T2WI, BPH nodules can be difficult to distinguish from cancer'''
**Lesion shape
**Lesion shape
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**#Volume ≥0.5cc and/or  
**#Volume ≥0.5cc and/or  
**#Extra prostatic extension(EPE).
**#Extra prostatic extension(EPE).
**'''<span style="color:#ff0000">Positive predictive values ISUP grade group ≥2 based on PI-RADS score:</span>[https://pubmed.ncbi.nlm.nih.gov/35393568/]'''
**'''Detection rates by PI-RADS score for any prostate cancer[https://pubmed.ncbi.nlm.nih.gov/37096582/]'''
*** '''PR 1-2: 15%'''
*** '''PR 3: 25%'''
*** '''PR 4: 58%'''
*** '''PR 5: 85%'''
**'''<span style="color:#ff0000">Positive predictive values for ISUP grade group ≥2 based on PI-RADS score:</span>[https://pubmed.ncbi.nlm.nih.gov/35393568/]'''
***'''<span style="color:#ff0000">PI-RADS 1-2: 7%[https://pubmed.ncbi.nlm.nih.gov/37096582/]</span>'''
***'''<span style="color:#ff0000">PI-RADS 3: 12–15%</span>'''
***'''<span style="color:#ff0000">PI-RADS 3: 12–15%</span>'''
***'''<span style="color:#ff0000">PI-RADS 4: 39–48%</span>'''
***'''<span style="color:#ff0000">PI-RADS 4: 39–48%</span>'''
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**Variable sensitivities (13-91%) and specificities (49-97%) have been reported for predicting extra-capsular extension.
**Variable sensitivities (13-91%) and specificities (49-97%) have been reported for predicting extra-capsular extension.


====== Guidelines on Use of MRI ======
====== Guidelines on Use of MRI Before Biopsy ======


* '''2023 NCCN (PROSD-3)'''
* '''2023 AUA Guidelines on Early Detection of Prostate Cancer'''
**'''Multiparametric MRI is strongly recommended, if available [before biopsy]'''
**'''<span style="color:#ff0000">May be used prior to initial biopsy to increase the detection of GG2+ prostate cancer[https://pubmed.ncbi.nlm.nih.gov/23659877/]</span>'''
***It is reasonable to obtain an mpMRI in biopsy-naïve patients prior to their first biopsy, but such a practice cannot be regarded as the standard approach based on the currently available evidence.
*'''2023 NCCN (PROSD-3)'''
**'''Multiparametric MRI is strongly recommended, if available'''
*'''2022 EAU[https://uroweb.org/guidelines/prostate-cancer/chapter/diagnostic-evaluation]'''
*'''2022 EAU[https://uroweb.org/guidelines/prostate-cancer/chapter/diagnostic-evaluation]'''
**'''Systematic biopsy is an acceptable approach in case MRI is unavailable'''  
**'''Systematic biopsy is an acceptable approach in case MRI is unavailable'''  
Line 463: Line 484:
**Authors' interpretation: Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy.
**Authors' interpretation: Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy.
**[https://pubmed.ncbi.nlm.nih.gov/32130814/ Ahdoot, Michael, et al.] "MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis." ''New England Journal of Medicine'' 382.10 (2020): 917-928.
**[https://pubmed.ncbi.nlm.nih.gov/32130814/ Ahdoot, Michael, et al.] "MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis." ''New England Journal of Medicine'' 382.10 (2020): 917-928.
*'''<span style="color:#ff00ff">GOTEBORG-2 (2022)</span>'''
*'''<span style="color:#ff00ff">GOTEBORG-2 (2022/2024)</span>'''
**Objective: Determine whether targeted-biopsy only (and avoid systematic) is adequate in patients with elevated PSA and prostate MRI
**Objective: Determine whether targeted-biopsy only (and avoid systematic) is adequate in patients with elevated PSA (3-10 ng/ml) and prostate MRI
**Population: Swedish males aged 50-60 living in Gothenburg, Sweden, without previous diagnosis of prostate cancer
**Population: Swedish males aged 50-60 living in Gothenburg, Sweden, without previous diagnosis of prostate cancer
**Randomized to invited screening with PSA test vs. no invitation
**Randomized to invited screening with PSA test vs. no invitation
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***Secondary outcome: detection of clinically significant prostate cancer, defined as a Gleason score of 3+4 or higher
***Secondary outcome: detection of clinically significant prostate cancer, defined as a Gleason score of 3+4 or higher
**Results:
**Results:
***17,980 (47%) of those randomized to invitation to screening underwent PSA testing
***19,733 (52%) of those randomized to invitation to screening underwent PSA testing
****7% had PSA > 3 ng/mL
****1371 (7%) had PSA > 3 ng/mL
*****95% of patients with PSA > 3 ng/mL underwent MRI
*****95% of patients with PSA > 3 ng/mL underwent MRI
***Clinically insignificant prostate cancer: significantly more common in patients undergoing systematic +/- targeted biopsy compared to targeted biopsy only (1.2% vs. 0.6%)
***Risk of clinically insignificant prostate cancer at screening or at interval: significantly more common in patients undergoing systematic +/- targeted biopsy compared to targeted biopsy only (2.4% vs. 1.0%)
***Clinically significant prostate cancer: no significant difference (1.1% systematic +/- targeted vs. 0.9% targeted biopsy only)
***Risk of clinically significant prostate cancer at screening or at interval: no significant difference (2.1% systematic +/- targeted vs. 1.8% targeted biopsy only)
***10 patients in reference group found to have clinically significant prostate cancer on systematic only
***(2022 publication) 10 patients in reference group found to have clinically significant prostate cancer on systematic only
****9 with negative MRI, 1 with false-positive MRI
****9 with negative MRI, 1 with false-positive MRI
*****All GG2, GG4 <5% in 6 patients
*****All GG2, GG4 <5% in 6 patients
******6 managed with AS
******6 managed with AS
***128 patients in experimental group with PSA <10 diagnosed with cancer by targeted biopsy only
***(2022 publication) 128 patients in experimental group with PSA <10 diagnosed with cancer by targeted biopsy only
****72/128 (56%) had GG1
****72/128 (56%) had GG1
*****86% underwent systematic biopsy
*****86% underwent systematic biopsy
*****26% upgraded (all GG2 except 1 to 3+5)
*****26% upgraded (all GG2 except 1 to 3+5)
****Gleason 3+3 lesions that had been detected by systematic biopsy differed only in tumor extension from those that had been detected by targeted biopsy of suspicious lesions shown on MRI, with greater volume measured in tumors that were visible on MRI
****Gleason 3+3 lesions that had been detected by systematic biopsy differed only in tumor extension from those that had been detected by targeted biopsy of suspicious lesions shown on MRI, with greater volume measured in tumors that were visible on MRI
**Author's interpretation: The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients.
**Author's interpretation: omitting prostate biopsy in men with negative MRI results, and thereby delaying a potential cancer diagnosis, was associated with a substantial reduction in the detection of clinically insignificant cancer and a very low risk of detecting incurable cancers at repeat screening rounds or as interval cancers.
**[https://pubmed.ncbi.nlm.nih.gov/39321360/ Hugosson, Jonas, et al.] "Results after Four Years of Screening for Prostate Cancer with PSA and MRI." ''New England Journal of Medicine'' 391.12 (2024): 1083-1095.
**[https://pubmed.ncbi.nlm.nih.gov/36477032/ Hugosson, Jonas, et al.] "Prostate cancer screening with PSA and MRI followed by targeted biopsy only." ''New England Journal of Medicine'' 387.23 (2022): 2126-2137.
**[https://pubmed.ncbi.nlm.nih.gov/36477032/ Hugosson, Jonas, et al.] "Prostate cancer screening with PSA and MRI followed by targeted biopsy only." ''New England Journal of Medicine'' 387.23 (2022): 2126-2137.


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* '''≈10%''' (but up to 20%) '''of negative MRI have clinically significant prostate cancer'''
* '''≈10%''' (but up to 20%) '''of negative MRI have clinically significant prostate cancer'''
* '''Predictors of clinically significant prostate cancer in presence of negative MRI'''
* '''Predictors of clinically significant prostate cancer in presence of negative MRI[https://pubmed.ncbi.nlm.nih.gov/31967522/]'''
** PSA density > 0.15 ng/ml/cc[https://pubmed.ncbi.nlm.nih.gov/30189186/][https://pubmed.ncbi.nlm.nih.gov/33080153/]
** PSA density > 0.15 ng/ml/cc[https://pubmed.ncbi.nlm.nih.gov/30189186/][https://pubmed.ncbi.nlm.nih.gov/33080153/]
** History of previous negative biopsy[https://pubmed.ncbi.nlm.nih.gov/30189186/]
** History of previous negative biopsy[https://pubmed.ncbi.nlm.nih.gov/30189186/]
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====== Prostate cancer PET radiopharmaceutical tracers ======
====== Prostate cancer PET radiopharmaceutical tracers ======
* '''Not PSMA-specific radiopharmaceutical tracers'''
* '''<span style="color:#ff0000">Not PSMA-specific radiopharmaceutical tracers'''
** Examples include 18F-fluciclovine (trade name Axumin), 18F-fluorodeoxyglucose (FDG), and 11C-choline
** Examples include '''<span style="color:#ff0000">18F-fluciclovine (trade name Axumin)</span>''', 18F-fluorodeoxyglucose (FDG), and 11C-choline
*** 18F-fluciclovine FDA approved in 2016
*** 18F-fluciclovine FDA approved in 2016
** '''Replaced by PSMA-specific tracers'''
** '''Replaced by PSMA-specific tracers'''
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****** Castrate-resistance
****** Castrate-resistance
** '''<span style="color:#ff0000">PSMA-specific radiopharmaceutical tracers used in prostate cancer (2):</span>'''
** '''<span style="color:#ff0000">PSMA-specific radiopharmaceutical tracers used in prostate cancer (2):</span>'''
***'''<span style="color:#ff0000">Fluorine-18 (18F)-labeled PSMA-specific</span>''' (18F-DCFPyL (trade name '''Pylarify'''), 18F-PSMA-1007)
***'''<span style="color:#ff0000">Fluorine-18 (18F)-labeled PSMA-specific</span>''' (18F-DCFPyL ('''piflufolastat''' F 18) (trade name '''<span style="color:#ff0000">Pylarify</span>'''), 18F-PSMA-1007)
****'''Most commonly used radiotracer in the US and''' (18F-DCFPyL) '''Canada'''
****'''Most commonly used radiotracer in the US and''' (18F-DCFPyL) '''Canada'''
****18F-DCFPyL adverse reactions: headache, altered taste, fatigue[https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer]
****18F-DCFPyL adverse reactions: headache, altered taste, fatigue[https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer]
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=== Other ===
=== Other ===


==== Risk calculators ====
==== Transrectal Ultrasound (TRUS) Biopsy ====
* Concept: improve prediction models by combining variables
* Patients with clinical indications to confirm diagnosis of prostate cancer undergo TRUS biopsy
* '''Most widely used in prostate cancer: [http://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators ERSPC] and [http://www.riskcalc.org/PCPTRC/ PCPT]'''
* '''Biopsy threshold'''
** [https://pubmed.ncbi.nlm.nih.gov/23659877/ '''2023 AUA Guidelines on Early Detection of Prostate Cancer''']
***'''<span style="color:#ff0000">May be tailored for select patients, similar to risk-stratified re-screening intervals</span>'''
****'''For patients with BRCA mutations, biopsy referral threshold should be 3 ng/mL'''
***'''<span style="color:#ff0000">Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy</span>'''
****Pre-biopsy Risk Calculators
***** Concept: improve prediction models by combining variables
***** [https://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators '''ERSPC''']
*****[https://riskcalc.org/PCPTRC/ '''PCPT V2''']
*****[https://riskcalc.org/PBCG/ '''PBCG''']
******'''In one study, investigators compared PBCG with PCPT and concluded that PCPT performed better in minority groups.'''
***PSA velocity should not be used as sole indication for secondary biomarker, imaging, or a biopsy.
***'''Adjunctive urine or serum markers may be used when further risk stratification would influence the decision regarding whether to proceed with biopsy.'''
****Several blood and urine markers are available, alone or in combination, to further risk stratify patients with a mildly elevated PSA, typically between 2.5 and 10 ng/mL.
*****'''Serum based'''
******'''Percent free PSA'''
*******Most widely available adjunctive test
*******Lower percent free PSA is associated with greater likelihood of identifying prostate cancer on biopsy.
******'''PSA density'''
*******Higher PSA density (serum PSA [ng/mL] divided by imaging measures of prostate volume [cc]) is associated with the risk of identifying clinically significant prostate cancer on biopsy
*******The Panel recognizes the continuous nature of risk associated with the spectrum of PSA density values and cautions against use of threshold values in isolation
******4Kscore
******IsoPSA
******Proclarix
******PHI
******STHLM-3
*****'''Urine based'''
******Post-DRE Urine
*******PCA3
*******MPS
*******SelectMDx
*******TMPRSS:ERG
******Urine
*******ExoDx Prostate Intelliscore
*******MiR Sentinel
******Tissue
*******Confirm MDx
*****Such tests may be of value among patients with modestly elevated PSA tests, especially in patients with a prior negative biopsy in whom PSA alone is not recommended as the sole trigger for rebiopsy.
*** '''When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy.'''
***<span style="color:#ff0000">'''Role of prostate biopsy in very elevated PSA'''</span>
****'''<span style="color:#ff0000">If PSA > 50 ng/mL </span>'''(and no clinical concerns for infection or other cause for increased PSA (e.g., recent prostate instrumentation)), '''<span style="color:#ff0000">may omit a prostate biopsy in cases if (2):</span>'''
*****'''<span style="color:#ff0000">Biopsy poses significant risk (e.g., anticoagulation, significant comorbidity, frailty)</span>'''
*****'''<span style="color:#ff0000">Need for prostate cancer treatment is urgent (e.g., impending spinal cord compression from metastases)</span>'''
****Imaging to establish extent of disease or confirm metastasis may be helpful if an immediate biopsy is not performed.
***'''If MRI performed prior to biopsy'''
****'''<span style="color:#ff0000">If no abnormal lesions on prostate MRI but concern for elevated risk for GG2+ prostate cancer, proceed with a systematic biopsy.</span>'''
*****≈1 in 10 patients who have a negative prostate MRI may have GG2+ cancer on biopsy,
******Negative predictive value (NPV) of a “negative” MRI (defined as PIRADS 1 to 2) to detect GG2+ prostate cancer among biopsy-naïve patients was 91%.
*****A systematic biopsy should include a minimum of 12 cores
*****Various templates employing these principles exist for transrectal and transperineal approaches.
****'''<span style="color:#ff0000">For biopsy-naïve patients with abnormal lesions on prostate MRI, perform targeted biopsies and may also perform a systematic template biopsy.</span>'''
*****Adding a systematic biopsy to the target only approach
******Advantage:
*******Optimizes cancer yield, potentially finding more GG2+ cancer
********Incremental yield of off-target biopsy samples may be influenced by the sampling error associated with software image registration at targeted biopsy
******Disadvantages:
*******Potentially finding more GG1 cancer
*******May increase patient discomfort and other biopsy-associated complications due to larger number of cores
***'''Repeat biopsy[https://pubmed.ncbi.nlm.nih.gov/23659877/]'''
****'''<span style="color:#ff0000">If prostate biopsy demonstrates</span>'''
*****'''<span style="color:#ff0000">Malignancy: discuss [[Management of Localized Prostate Cancer]]</span>''' (+/- staging studies, if applicable)
*****'''<span style="color:#ff0000">High-grade Prostatic Intraepithelial Neoplasia</span>'''
******'''<span style="color:#ff0000">If focal (one core): should not perform immediate repeat biopsy.</span>'''
*******Risk of any cancer detected (not just high-grade) in subsequent biopsies is 20-30%, which is the same risk following an initial benign biopsy.
******'''<span style="color:#ff0000">Multifocal: may proceed with additional risk evaluation.</span>'''
*******Risk of GG2+ detection in repeat biopsies of patients with multifocal HGPIN is ≈30%, which is not higher than in those without this finding.
*******Repeat biopsy after multifocal HGPIN should be based on PSA and DRE evolution, and mpMRI findings.
*****'''<span style="color:#ff0000">Atypia</span>'''
******'''<span style="color:#ff0000">Atypical small acinar proliferation (ASAP): should perform additional testing.</span>'''
*******ASAP alone on needle biopsy is associated with a 30-50% risk of prostate cancer detection on repeat biopsy, with ≈10-20% of these being GG2+.
*******Additional testing may include repeat systematic needle biopsy with consideration of mpMRI +/- targeted biopsy, PSA, and biomarkers (serum- or urine-based)
******'''<span style="color:#ff0000">Atypical intraductal proliferation (AIP): should perform additional testing.</span>'''
*******AIP describes lesions with greater architectural complexity and/or cytologic atypia than would be expected in HGPIN but lacking definitive criteria for the diagnosis of intraductal carcinoma (IDC-P). AIP encompasses many of the lesions formerly designated cribriform HGPIN, exhibiting loose cribriform architecture with moderate cytologic atypia, but lacking marked pleomorphism or necrosis.
*******AIP, as either the sole finding or together with GG1 cancer only, warrants additional testing, which may include early repeat systematic needle biopsy or MRI +/- targeted biopsy. The timing of additional testing should be based on reassessment of risk
*****'''<span style="color:#ff0000">Negative: reassess risk of undetected or future development of GG2+ disease</span>'''
******'''<span style="color:#ff0000">At the time of re-evaluation after negative biopsy, clinicians should use a risk assessment tool that incorporates the protective effect of prior negative biopsy.</span>'''
*******The guideline recommends utilizing validated risk calculators, particularly calculators that incorporate previous negative biopsy and mpMRI use in the repeat biopsy setting.
********[https://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators ERSPC]
********[https://riskcalc.org/PCPTRC/ PCPT V2]
********[https://riskcalc.org/PBCG/ PBCG]
*******PSA level alone should not be used to decide whether to repeat the prostate biopsy in patients with a previous negative biopsy.
******'''<span style="color:#ff0000">Based on risk assessment, SDM whether to</span>'''
*******'''<span style="color:#ff0000">Discontinue screening</span>'''
********'''Screening should not be discontinued based solely on a negative prostate biopsy.'''
*******'''<span style="color:#ff0000">Continue screening</span>'''
********If continuing screening after a negative biopsy, patient should be re-evaluated within the normal screening interval (2-4 years) or sooner, depending on risk of clinically significant prostate cancer and life expectancy.
*******'''<span style="color:#ff0000">Perform adjunctive testing for early reassessment of risk.</span>'''
********If concern remains elevated for GG2+ based on PSA density, previous MRI findings, or other factors,  consider adjunctive testing (blood, urine, or tissue tests), or MRI (if not previously performed) to further risk stratify the patient if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the patient’s management.
*********'''Biomarker testing'''
**********After a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer, clinicians should not reflexively perform biomarker testing.
***********In patients with a negative biopsy, with low probability for GG2+ disease, it is unlikely that additional biomarker tests will be informative.
**********ConfirmMDx
***********The only tissue-based biomarker assessing epigenetic changes in GSTP1, APC, RASSF1 in negative biopsy tissue
***********Developed in the MATLOC study and validated in the DOCUMENT study to detect any prostate cancer and not specifically for GG2+ disease.
**********Unclear how to integrate the use of these tests with mpMRI in prostate cancer early detection.
**********It is imperative clinicians are familiar with biomarkers, understand what information or data each test provides, and consider whether additional information will impact  management decisions before ordering a test.
*********'''<span style="color:#ff0000">MRI prior to repeat biopsy</span>'''
**********'''<span style="color:#ff0000">In patients undergoing repeat biopsy with no prior prostate MRI, a prostate MRI should be obtained prior to biopsy.</span>'''
**********'''<span style="color:#ff0000">In patients with indications for a repeat biopsy who</span>'''
***********'''<span style="color:#ff0000">Do not have a suspicious lesion on MRI, may proceed with a systematic biopsy.</span>'''
************Factors that may identify patients likely to have clinically significant prostate cancer after a negative biopsy and a negative MRI include
*************PSA density > 0.15 ng/mL
*************PHI density value > 0.44
*************PSA velocity of ≥0.27 ng/mL/year
***********'''<span style="color:#ff0000">Have a suspicious lesion on MRI, should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy.</span>'''
************Ultimately, the decision to perform systematic sampling in addition to target sampling should be based on an integrated evaluation of MRI factors such as quality and confidence in target presence and clinical factors such as PSA, technique of initial biopsy, and time since prior systematic biopsy.
 
*'''The choice of a PSA threshold for recommending a prostate biopsy is controversial'''.
** Historically, many would recommend prostate biopsy once a patient’s serum PSA level is >4.0 ng/mL. However, '''data from the Prostate Cancer Prevention Trial demonstrated an overall prostate cancer detection rate of 15% for all men with a PSA level < 4.0 ng/mL and nearly 15% having a Gleason score of 7 or greater, suggesting no absolute safe threshold.'''


==== Genetic testing ====
==== Genetic testing ====
* Germline mutations are inherited from parents; all cells have the mutation except red blood cells
* Germline mutations are inherited from parents; all cells have the mutation except red blood cells
*Somatic mutations are acquired
*Somatic mutations are acquired
* '''Indications'''
** '''NCCN (version 2.2021)'''
*** '''Recommended (5)'''
***# '''Metastatic (distant or regional (node-positive) prostate cancer'''
***# '''High- or very-high risk localized prostate cancer'''
***# '''Personal history of breast cancer'''
***# '''Positive family history of high-risk germline mutations (e.g. BRCA 1/2, Lynch syndrome)'''
***#* '''BRCA-cancers (5): breast, ovarian, pancreatic, prostate, melanoma'''
***#* '''Lynch syndrome cancers: (8) colonic (most common), endometrial (second most common), prostate, urothelial, adrenal, gastric, pancreatic, uterine, ovarian, and sebaceous carcinomas'''
***# '''Ashkenazi Jewish ancestry'''
*** '''Optional (2)'''
***# '''Intermediate-risk with intraductal or cribiform histology'''
***# '''Personal history of colorectal, gastric, melanoma, uppert tract urothelial, glioblastoma, biliary tract, or small intestine'''


==== Transrectal Ultrasound (TRUS) Biopsy ====
===== Indications =====
* Patients with clinical indications to confirm diagnosis of prostate cancer undergo '''TRUS biopy'''
 
* '''Triggers for biopsy'''
====== AUA ======
** '''A PSA level that is considered suspicious for prostate cancer should be remeasured before performing a prostate biopsy because of fluctuations in PSA levels that could create false-positive elevations.'''
* '''[https://pubmed.ncbi.nlm.nih.gov/35536144/ 2022 AUA Guidelines on Clinically Localized Prostate Cancer]'''
*** According to the AUA Choosing Wisely Campaign, empirical antibiotics should not be given to patients exclusively for an elevated PSA without any other urinary symptoms
** '''<span style="color:#ff0000">Recommended (5):'''
** '''The choice of a PSA threshold for recommending a prostate biopsy is controversial'''.
**# '''<span style="color:#ff0000">Ashkenazi Jewish ancestry'''
*** Historically, many would recommend prostate biopsy once a patient’s serum PSA level is >4.0 ng/mL. However, '''data from the Prostate Cancer Prevention Trial demonstrated an overall prostate cancer detection rate of 15% for all men with a PSA level < 4.0 ng/mL and nearly 15% having a Gleason score of 7 or greater, suggesting no absolute safe threshold.'''
**#* '''Particularly in patients with Grade Group 2 or higher disease'''
** Numerous organizations now recommend using PSA together with other methods of risk assessment, such as family history, race, DRE findings, and risk calculators
**# '''<span style="color:#ff0000">Known family history of familial cancer risk mutation'''
**#* '''Examples: BRCA1, BRCA2, ATM, Lynch-syndrome associated genes'''
**# '''<span style="color:#ff0000">Strong personal or family history of related cancers'''
**#* '''Examples: breast, colorectal, ovarian, pancreatic, upper tract urothelial carcinoma'''
**# '''<span style="color:#ff0000">Strong family history of prostate cancer'''
**#* '''Examples: first-degree relative or multiple second-degree relatives diagnosed with Grade Group 2 or higher prostate cancer, particularly at early age (< 60 years), particularly if metastatic or lethal'''
**# '''<span style="color:#ff0000">Adverse tumor characteristics'''
**#* '''Examples: High-risk disease; intermediate-risk disease with intraductal or cribriform morphology'''
 
====== NCCN ======
*'''NCCN (version 2.2021)'''
** '''<span style="color:#ff0000">Recommended (5):'''
**# '''<span style="color:#ff0000">Ashkenazi Jewish ancestry'''
**#'''<span style="color:#ff0000">Positive family history of high-risk germline mutations (e.g. BRCA 1/2, Lynch syndrome)'''
**#* '''BRCA-cancers (5): breast, ovarian, pancreatic, prostate, melanoma'''
**#* '''Lynch syndrome cancers: (8) colonic (most common), endometrial (second most common), prostate, urothelial, adrenal, gastric, pancreatic, uterine, ovarian, and sebaceous carcinomas'''
**#'''<span style="color:#ff0000">Personal history of breast cancer'''
**#'''<span style="color:#ff0000">Metastatic (distant or regional (node-positive) prostate cancer'''
**# '''<span style="color:#ff0000">High- or very-high risk localized prostate cancer'''
** '''Optional (2)'''
**# '''Intermediate-risk with intraductal or cribiform histology'''
**# '''Personal history of colorectal, gastric, melanoma, upper tract urothelial, glioblastoma, biliary tract, or small intestine'''
 
==== Stockholm-3 (STHLM-3) ====
*Multiplex test combining
**Clinical variables (age, first-degree family history of prostate cancer, and previous biopsy)
**Blood biomarkers (total PSA, free PSA, ratio of free to total PSA, hK2, MIC-1, and MSMB)
**Polygenic risk score (PRS)
*Has been evaluated as a first-line screening test for predicting the risk of GG2+ prostate cancers.[https://pubmed.ncbi.nlm.nih.gov/26563502/]
**STHLM-3 found to have a higher predictive accuracy compared to PSA alone (area under the curve [AUC] 0.74 versus 0.56) and reduced unnecessary biopsies by 32%
** Further validation in diverse populations to confirm these findings will be necessary to move forward into practice.
 
==== Polygenic risk score (PRS) ====


* Genetic tests used to predict a person’s risk of developing prostate cancer.
*Typically constructed as the weighted sum of a collection of genetic variants, usually single nucleotide polymorphisms (SNPs) defined as single base-pair variations from the reference genome[https://pubmed.ncbi.nlm.nih.gov/35251129/]
*Little evidence to mandate which SNP panel or PRS to use and where to threshold risk to create strata with different screening intensities.
*At the time of evidence review, no PRS tool has been shown to discriminate between aggressive and indolent prostate cancer risk
== Questions ==
== Questions ==


Line 689: Line 842:
#*Bound to 3 proteins: α1-antichymotripson, α2-macroglobulin, α1-protease inhibitor
#*Bound to 3 proteins: α1-antichymotripson, α2-macroglobulin, α1-protease inhibitor
#When does serum PSA become detectable?
#When does serum PSA become detectable?
##Puberty
#*Puberty
#What is the optimal MRI sequence to evaluate
#What is the optimal MRI sequence to evaluate
## Hemorrhage
## Hemorrhage
Line 704: Line 857:
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 108
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 108
*Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 111
*Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 111
* AUA Update Series (2016) Lesson 14: Multiparametric Magnetic Resonance Imaging for Prostate Cancer
* [https://pubmed.ncbi.nlm.nih.gov/12525533/ Balk, Steven P., Yoo-Joung Ko, and Glenn J. Bubley.] "Biology of prostate-specific antigen." ''Journal of clinical oncology'' 21.2 (2003): 383-391.
*AUA Update Series (2016) Lesson 14: Multiparametric Magnetic Resonance Imaging for Prostate Cancer
* [https://pubmed.ncbi.nlm.nih.gov/33661093/ Shaygan, Bobby, et al.] "Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer." ''Canadian Urological Association Journal'' 15.6 (2021): 162.
* [https://pubmed.ncbi.nlm.nih.gov/33661093/ Shaygan, Bobby, et al.] "Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer." ''Canadian Urological Association Journal'' 15.6 (2021): 162.